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Scientists Watch Activity of Newborn Brain Cells in Mice; Reveal they are Required for Memory
Columbia neuroscientists have described the activity of newly generated brain cells in awake mice—a process known as adult neurogenesis—and revealed the critical role these cells play in forming memories. The new research also offers clues as to what happens when the memory-encoding process goes awry.
This study, led by researchers at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute and Columbia University Medical Center (CUMC), was published in Neuron.
“Our approach allows us to compare the activity of newborn and mature cells in the brains of behaving animals,” said Attila Losonczy, MD, PhD, a principal investigator at Columbia’s Zuckerman Institute, assistant professor of neuroscience at CUMC and a senior author of the paper. “These findings could help scientists decipher the role that adult neurogenesis plays in both health and disease.”
Most brain cells are produced before birth, but a few select brain regions continue to grow new cells into adulthood. One such region is called the dentate gyrus, a tiny structure in the hippocampus, the brain’s headquarters for learning and memory. But because the dentate gyrus is so small, and buried so deeply within the brain, scientists have had difficulty studying it.
“One of the great unanswered questions in neuroscience is, why did nature decide to replenish cells in this region of the brain, but not others?” said Dr. Losonczy. “In this study, we developed sophisticated and refined methods to investigate this question more thoroughly than ever before.”
Earlier studies suggested that cells within the dentate gyrus, known as granule cells, allow the brain to distinguish between similar, yet different, environments. This process, known as pattern separation, is a key component of the brain’s internal GPS. It helps us remember where we parked the car this morning, versus where we parked two weeks ago, for example.
“Most granule cells are present in the dentate gyrus from birth, but a small percentage are the result of adult neurogenesis, which churns out fresh granule cells into adulthood,” said René Hen, PhD, professor of neuroscience and pharmacology (in psychiatry) at CUMC and a senior author of the paper. “We hypothesized that these so-called adult-born granule cells play a crucial role in pattern separation.”
Using a two-photon microscope, the researchers observed the activity of adult-born granule cells in the brains of mice as they walked along a treadmill. In order to induce the formation of new memories, this treadmill was lined with distinct textures and surrounded by different multisensory cues. The scientists were able to map how both types of granule cells—the new, adult-born cells as well as the old, mature cells—were involved in pattern separation.
“Other studies had been unable to image the dentate gyrus, let alone the individual cells that reside within it, at this level of detail,” said Mazen Kheirbek, PhD, the paper’s last author who completed this work while at Columbia. “Here, we were able to demonstrate that adult-born granule cells act differently than their mature neighbors, and determine why that difference is so critical.”
The difference, the researchers found, lies in the adult-born cells’ unique activity pattern. Shortly after they are produced, adult-born granule cells exhibit heightened excitability compared with their mature counterparts. But after six weeks, this activity drops off. The initial burst of excitability, the authors postulated, could be key to capturing the memories required for pattern separation.
To determine what happens when this process is disrupted, the researchers placed the mice in one environment and gave them a small footshock. Then, they introduced the animals to a second, safe, environment that was similar, yet distinct, from the first. Using optogenetics—a technique that uses laser light to manipulate specific brain cells—the scientists temporarily silenced the adult-born granule cells during exposure to the safe environment. A normal, healthy mouse could distinguish between the two settings and exhibited a fear response to the unfavorable environment. But to the mice with the silenced brain cells, both environments—both dangerous and safe—appeared the same, causing the mice to fear both environments.
“These findings reveal that adult-born granule cells are required not only to encode the memory of a new experience, but also to determine whether one experience is different from the next,” said Dr. Kheirbek. “The merging of memories, which is what we observed when the adult-born cells were silenced, is a key feature of a wide range of psychiatric conditions—from anxiety and mood disorders to post-traumatic stress disorder.”
“Indeed, the inability to discriminate between two distinct, but similar events—such as a gunshot versus a car backfiring—is often seen in these disorders,” said Dr. Hen. “Understanding how adult-born granule cells impact behavior in the living brain is an important step toward one day harnessing this process for therapeutic purposes.”
Worlds That Will Make You Believe Star Wars is Real
The fantastical planets in Star Wars preceded our discovery of real planets outside our solar system…but fiction isn’t too far from the facts. When we send our spacecraft into the solar system and point our telescopes beyond, we often see things that seem taken right out of the Star Wars universe.
Is there a more perfect time than May the 4th to compare real worlds to the ones depicted in Star Wars?
Probably not…so here are a few:
Mimas
Saturn’s moon, Mimas, has become known as the “Death Star” moon because of how its 80-mile wide Herschel crater creates a resemblance to the Imperial battle station, especially when seen in this view from our Cassini spacecraft.
Kepler-452b
The most recently revealed exoplanet dubbed as Earth’s bigger, older cousin, Kepler-452b, might make a good stand-in for Coruscant — the high tech world seen in several Star Wars films whose surface is encased in a single, globe-spanning city. Kepler-452b belongs to a star system 1.5 billion years older than Earth’s! That would give any technologically adept species more than a billion-year jump ahead of us.
CoRoT-7B
At 3,600 degrees Fahrenheit, CoRoT-7B is a HOT planet. Discovered in 2010 with France’s CoRoT satellite, it’s some 480 light-years away, and has a diameter 70% larger than Earth’s, with nearly five times the mass. Possibly the boiled-down remnant of a Saturn-sized planet, its orbit is so tight that its star looms much larger in its sky than our sun appears to us, keeping its sun-facing surface molten!
Kepler-16b
Luke Skywalker’s home planet, Tatooine, is said to possess a harsh, desert environment, swept by sandstorms as it roasts under the glare of twin suns. Real exoplanets in the thrall of two or more suns are even harsher! Kepler-16b was the Kepler telescope’s first discovery of a planet in a “circumbinary” orbit (a.k.a, circling both stars, as opposed to just one, in a double star system). This planet, however, is likely cold, about the size of Saturn, and gaseous, though partly composed of rock.
OGLE-2005-BLG-390
Fictional Hoth is a frozen tundra that briefly serves as a base for the hidden Rebel Alliance. It’s also the nickname of real exoplanet OGLE-2005-BLG-390, a cold super-Earth whose surface temperature clocks in at minus 364 degrees Fahrenheit.
Kepler-22b
Kepler-22b, analog to the Star Wars planet Kamino…which was the birthplace of the army of clone soldiers, is a super-Earth that could be covered in a super ocean. The jury is still out on Kepler-22b’s true nature; at 2.4 times Earth’s radius, it might even be gaseous. But if the ocean world idea turns out to be right, we can envision a physically plausible Kamino-like planet.
Gas Giants
Gas giants of all stripes populate the real exoplanet universe; in Star Wars, a gas giant called Bespin is home to a “Cloud City” actively involved in atmospheric mining. Mining the atmospheres of giant gas planets is a staple of science fiction. We too have examined the question, and found that gases such as helium-3 and hydrogen could theoretically be extracted from the atmospheres of Uranus and Neptune.
Exomoons
Endor, the forested realm of the Ewoks, orbits a gas giant. Exomoon detection is still in its infancy for scientists on Earth. However, a possible exomoon (a moon circling a distant planet) was observed in 2014 via microlensing. It will remain unconfirmed, however, since each microlensing event can be seen only once.
May the 4th be with you!
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I got "Carried" away. Lol Blubonicplague1
Star Wars!
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